Of mice and men: how related are we?

All life on Earth shares a single common ancestor, but is it possible to measure our genetic similarities accurately?

It's difficult to get one's head around the idea that all life on Earth shares a single common ancestor. Biologists tell us we can measure specific genomic commonalities between species, which illustrates how all species are in some way related. According to one source, we share about 98 per cent of our DNA with chimpanzees, 85 per cent with the zebrafish and 36 per cent with a fruit fly. We even share 3 per cent with E.coli.

"The 98 per cent number often quoted for the chimpanzee is found by aligning the DNA sequence of the chimp genome to the human genome," says Prof Ken Wolfe of the Wolfe Laboratory at University College Dublin. "We know that 98.7 per cent of the bases in the chimp genome are identical to the corresponding base in the human genome. The other 1.3 per cent are different, indicating nucleotide substitutions that occurred during evolution.

“In addition to these nucleotide substitutions, a small fraction (about 1 per cent) of the human and chimp genomes are not alignable to each other, due to insertions or deletions of chunks of DNA since our last shared ancestor. These insertions/ deletions generally don’t affect genes; they are ‘noncoding’ DNA.”

Humans and chimps

It is easy, relatively speaking, to compare humans and chimps. When one moves to more distant comparisons, however, the DNA sequence becomes more divergent, and less of the genome is alignable.

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"With humans and chimps, the average is quite representative and most of the DNA is similar," says Dr Aoife McLysaght of the Smurfit Institute of Genetics at Trinity College Dublin. "It's when you get to other creatures that making comparisons starts to get difficult. Just reporting the average similarity masks the fact that there are genes with extremely low and extremely high similarity, and lots of genes where we can't find any match at all."

An orphan gene is so called because no ancestors can be found for it. “The reason for this is that it’s either a brand-new gene, so it has no ancestors, or its genetic relationship with other genes is hard to detect because the two are so far diverged,” says McLysaght. Orphan genes complicate attempts to put hard-and-fast figures on the genetic make-up of a species. And that’s just one hurdle.

In reality, genomic comparisons only truly work where there is similarity in function.

“Shared genes are called orthologues,” says Wolfe. “For example, the human insulin gene and the mouse insulin-1 gene are orthologues. They both code for insulin hormones in their respective species, and the functions of the genes are identical, but their DNA sequences are only 81 per cent identical due to the accumulation of nucleotide substitutions during the 100 million years since humans and mice diverged from their shared ancestor.

“Different genes evolve at different rates, depending on what their functions are. Insulin has a fairly average rate.”

The trick, therefore, is to choose the appropriate level of comparison for the question you want to ask.

Racing-car analogy

"One analogy might be that you can sensibly try to understand the fundamental principles of racing cars by comparing a modern Formula One car, part by part, with a 1930s Bugatti, but not with a Roman racing chariot," says Dr Andrew Flaus of the centre for chromosome biology at NUI Galway. "Chariots and Formula One cars have wheels and a cockpit space, and share the general aim of going fast around a track. However, so much has been evolved for their separate niches, and through happenstance evolutionary pathways, that you can no longer draw clear links between many of the pieces, even though some have broadly similar overall functions (for example, combustion engines and horses)."

One way to get around the problem of making links is through gene ontology. “It enables weak lines to be drawn and built up as best we can, based on a uniform dictionary for describing things,” says Flaus. “In our analogy, the horse and combustion engine would be tagged with the function of ‘motive force’ from our racing-car ontology.”

Gene ontology simplifies genetic differences in order to make what is a hugely complicated area more digestible. Likewise, attributing simplistic percentages to compare DNA is almost like an exercise in biological housekeeping: neat and tidy, but not necessarily clean.

“It’s a useful way of conveying how similar species are,” says McLysaght. “The more distantly related the animals, the more genetic differences you’ll find. That’s an accurate concept. You could argue about numbers all the way down the scale, but when two species diverge significantly, there’s really not much point. The central idea holds: closer evolutionary relatives have more similar DNA sequences.”

THE NEAR YEAST: YOU HAVE YOUR MOTHER’S PIES

Baker's yeast and humans share many genetic similarities. Baker's yeast (Saccharomyces cerevisiae) shared a common ancestor with humans about a billion years ago. A distant relationship, no doubt, but nevertheless molecular biologists at the University of Texas at Austin have found that there are thousands of genes shared between humans and yeast.

The researchers conducted experiments and found a significant number of human genes that can replace their faulty counterparts in yeast and stop the micro-organisms from dying. They carried out 400 human-to-yeast gene replacements, and half were able to compensate for a missing vital function in the defective yeast.

“It’s a beautiful demonstration of the common heritage of all living things,” says Edward Marcotte, professor in the university’s department of molecular biosciences.

The similarities between human beings and their morning toast don’t end there.

“There is a gene called histone 4 that is almost identical between humans and wheat,” says Dr Aoife McLysaght of the Smurfit Institute of Genetics in Trinity College Dublin. “There are only 55 differences in the DNA sequence of the entirety of the gene.

At the protein level, there are only two differences between the entire human and wheat protein. In other words, the wheat protein in your sandwich is almost identical to its human counterpart.

“The fact that it’s so similar means it’s not random,” says McLysaght. “Because of natural selection, almost any change to that gene would cause the organism to die. This is not to say that change doesn’t happen; it’s that change doesn’t survive the elimination of bad mutations. When we talk about highly similar genes, we are referring to those with clear evolutionary constraints. So it is no surprise that those genes are replaceable between humans and wheat.”

John Holden

John Holden

John Holden is a contributor to The Irish Times specialising in science, technology and innovation